한빛사논문
- 조회781
Sehoon Park1,2, Soojin Lee3,4,5, Yaerim Kim6, Semin Cho3,4, Kwangsoo Kim7, Yong Chul Kim3, Seung Seok Han3,8, Hajeong Lee3, Jung Pyo Lee3,8,9, Soryoung Lee3,4, Eue-Keun Choi3,4, Kwon Wook Joo3,4,8, Chun Soo Lim3,8,9, Yon Su Kim1,3,4,8 and Dong Ki Kim3,4,8,*
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. 2Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, Seongnam, Korea. 3Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea. 4Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. 6Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea. 7Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea. 8Kidney Research Institute, Seoul National University, Seoul, Korea. 9Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
*Correspondence to Dong Ki Kim.
Abstract
Background
Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis.
Methods
The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR.
Results
A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome.
Conclusions
This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.
논문정보
- Research article
- 2021년 11월 (BRIC 등록일 2021-11-26)
- 국내 연구진
- 의약학 > 응용의학
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